Activation Pathways and Free Energy Landscapes of the SARS-CoV-2 Spike Protein.

ACS Omega
Yichao WuWei Wang


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses a spike protein (S-protein) to recognize the receptor protein ACE2 of human cells and initiate infection, during which the conformational transition of the S-protein from inactive (down) state to active (up) state is one of the key molecular events determining the infectivity but the underlying mechanism remains poorly understood. In this work, we investigated the activation pathways and free energy landscape of the S-protein of SARS-CoV-2 and compared with those of the closely related counterpart SARS-CoV using molecular dynamics simulations. Our results revealed a large difference between the activation pathways of the two S-proteins. The transition from inactive to an active state for the S-protein of SARS-CoV-2 is more cooperative, involving simultaneous disruptions of several key interfacial hydrogen bonds, and the transition encounters a much higher free energy barrier. In addition, the conformational equilibrium of the SARS-CoV-2 S-protein is more biased to the inactive state compared to that of the SARS-CoV S-protein, suggesting the transient feature of the active state before binding to the receptor protein of the host cell. The key interactions contribu...Continue Reading


Dec 3, 2008·The Journal of Chemical Physics·Michael R Shirts, John D Chodera
Jan 9, 2010·The Journal of Physical Chemistry. B·Justin A Lemkul, David R Bevan
Jul 26, 2013·The Journal of Chemical Physics·Ryuhei Harada, Akio Kitao
Dec 3, 2014·Biochimica Et Biophysica Acta·Rafael C BernardiKlaus Schulten
Sep 1, 2016·Annual Review of Virology·Fang Li
Aug 1, 2019·Nature Methods·UNKNOWN PLUMED consortium
Dec 25, 2019·Physical Review. E·Jianyang KongWei Wang
Jan 25, 2020·The New England Journal of Medicine·Na ZhuUNKNOWN China Novel Coronavirus Investigating and Research Team
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Mar 1, 2020·International Journal of Surgery·Catrin SohrabiRiaz Agha
May 8, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jian ShangFang Li
May 29, 2020·The Journal of Physical Chemistry Letters·Angelo SpinelloAlessandra Magistrato
Jun 7, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yingjie WangJiali Gao
Jul 24, 2020·Nature Structural & Molecular Biology·Rory HendersonPriyamvada Acharya
Aug 14, 2020·The Journal of Physical Chemistry. B·Hoang Linh NguyenMai Suan Li
Aug 24, 2020·The Journal of Chemical Physics·Mert GurMert Golcuk
Nov 3, 2020·Trends in Immunology·Andrew G HarrisonPenghua Wang
Nov 4, 2020·ACS Central Science·Lorenzo CasalinoRommie E Amaro
Nov 11, 2020·Lung·Filippo ScialoAndrea Bianco
Dec 12, 2020·Cell·Alexandra C WallsDavid Veesler
Feb 24, 2021·Journal of Chemical Information and Modeling·Frederico Campos FreitasRonaldo Junio de Oliveira
Apr 10, 2021·Journal of Medicinal Chemistry·Binquan Luan, Tien Huynh
Apr 18, 2021·Physical Review. E·Wentao ZhuWei Wang
Aug 21, 2021·Nature Chemistry·Terra SztainRommie E Amaro

❮ Previous
Next ❯

Related Concepts

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.


Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.


Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.